Oligodendroglia are limited in type I interferon induction and responsiveness in vivo
Article first published online: 26 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 60, Issue 10, pages 1555–1566, October 2012
How to Cite
Kapil, P., Butchi, N. B., Stohlman, S. A. and Bergmann, C. C. (2012), Oligodendroglia are limited in type I interferon induction and responsiveness in vivo. Glia, 60: 1555–1566. doi: 10.1002/glia.22375
- Issue published online: 16 AUG 2012
- Article first published online: 26 JUN 2012
- Manuscript Accepted: 31 MAY 2012
- Manuscript Received: 11 JAN 2012
- National Institute of Health. Grant Number: P01 NS064932
- central nervous system;
- innate immunity;
Type I interferons (IFNα/β) provide a primary defense against infection. Nevertheless, the dynamics of IFNα/β induction and responsiveness by central nervous system (CNS) resident cells in vivo in response to viral infections are poorly understood. Mice were infected with a neurotropic coronavirus with tropism for oligodendroglia and microglia to probe innate antiviral responses during acute encephalomyelitis. Expression of genes associated with the IFNα/β pathways was monitored in microglia and oligodendroglia purified from naïve and infected mice by fluorescent activated cell sorting. Compared with microglia, oligodendroglia were characterized by low basal expression of mRNA encoding viral RNA sensing pattern recognition receptors (PRRs), IFNα/β receptor chains, interferon sensitive genes (ISG), as well as kinases and transcription factors critical in IFNα/β signaling. Although PRRs and ISGs were upregulated by infection in both cell types, the repertoire and absolute mRNA levels were more limited in oligodendroglia. Furthermore, although oligodendroglia harbored higher levels of viral RNA compared with microglia, Ifnα/β was only induced in microglia. Stimulation with the double stranded RNA analogue poly I:C also failed to induce Ifnα/β in oligodendroglia, and resulted in reduced and delayed induction of ISGs compared with microglia. The limited antiviral response by oligodendroglia was associated with a high threshold for upregulation of Ikkε and Irf7 transcripts, both central to amplifying IFNα/β responses. Overall, these data reveal that oligodendroglia from the adult CNS are poor sensors of viral infection and suggest they require exogenous IFNα/β to establish an antiviral state. © 2012 Wiley Periodicals, Inc.